Pima Indians have a high prevalence of obesity, diabetes mellitus, and hyperinsulinemia, but they have low plasma cholesterol levels, reduced low density lipoprotein (LDL) and high density lipoprotein (HDL), and decreased incidence of cardiovascular disease (CVD). Lipoprotein composition and metabolism in Pima Indians are being investigated in order to further understand control of lipoprotein metabolism and how lipoproteins are related to obesity and CVD. A multicompartmental model has been developed for the analysis of kinetic data for the simultaneous measure of VLDL, IDL, and LDL apoB metabolism. Comparsion of apoB metabolism in Pimas and weight-matched Caucasians indicated that the low LDL in Pimas is related to both higher FCR for LDL and higher proportion of VLDL metabolized without conversion to LDL. The results of lipoprotein metabolism studies suggest a large flux of substrates and regulators (e.g., insulin) which cause overproduction of lipoproteins, but that compensatory mechanisms are operative which result in maintenance of low plasma concentrations. In order to understand the reason for the lack of sex differences in HDL in the Pimas, we have studied HDL composition, lipase activities, and steroid hormone concentrations. The data indicated that obesity in this population has a stronger influence on both concentrations and composition of HDL in women. The change in HDL in obese women was associated with decreases in levels of plasma estradiol and increases in hepatic lipase activities. Since there are so few lean women in the Pima population, the net result is that HDL levels in women in the population as a whole do not differ from those of men.